Juan Su1,2, Zhanquan Li1,2, Sen Cui1,2, Linhua Ji1,2, Hui Geng1,2, Kexia Chai1,2, Xiaojing Ma1,2, Zhenzhong Bai1, Yingzhong Yang1, Tana Wuren1, Ri-Li Ge1, Matthew T Rondina3. 1. 1 Research Center for High Altitude Medicine, Qinghai University , Xining, China . 2. 2 Department of Hematology, Qinghai University Affiliated Hospital , Xining, China . 3. 3 Division of General Internal Medicine and University Healthcare Thrombosis Service, Department of Internal Medicine, University of Utah Health Sciences Center , Salt Lake City, Utah.
Abstract
AIM: Chronic mountain sickness (CMS) is characterized by excessive erythrocytosis, and angiogenesis may be involved in the pathogenesis of this disease. The bone marrow niche is the primary site of erythropoiesis and angiogenesis. This study was aimed at investigating the associations of the levels of hypoxia-inducible factors (HIFs), erythropoietin (EPO), and erythropoietin receptor (EPOR), as well as microvessel density (MVD) in the bone marrow with CMS. RESULTS: A total of 34 patients with CMS and 30 control subjects residing in areas at altitudes of 3000-4500 m were recruited for this study. The mRNA and protein expression of HIF-2α and EPO in the bone marrow cells was significantly higher in the CMS patients than in the controls. Moreover, changes in HIF-2α expression in CMS patients were significantly correlated with EPO and hemoglobin levels. In contrast, the expression of mRNA and protein expression of HIF-1α and EPOR did not differ significantly between the CMS and control patients. Increased MVD was observed in the bone marrow of the patients with CMS and it was significantly correlated with hemoglobin. CONCLUSIONS: Bone marrow cells of CMS patients may show enhanced activity of the HIF-2α/EPO pathway, and EPO may regulate the erythropoiesis and vasculogenesis through autocrine or/and paracrine mechanisms in the bone marrow niche. The increased MVD in the bone marrow of CMS patients appears to be involved in the pathogenesis of this disease.
AIM: Chronic mountain sickness (CMS) is characterized by excessive erythrocytosis, and angiogenesis may be involved in the pathogenesis of this disease. The bone marrow niche is the primary site of erythropoiesis and angiogenesis. This study was aimed at investigating the associations of the levels of hypoxia-inducible factors (HIFs), erythropoietin (EPO), and erythropoietin receptor (EPOR), as well as microvessel density (MVD) in the bone marrow with CMS. RESULTS: A total of 34 patients with CMS and 30 control subjects residing in areas at altitudes of 3000-4500 m were recruited for this study. The mRNA and protein expression of HIF-2α and EPO in the bone marrow cells was significantly higher in the CMSpatients than in the controls. Moreover, changes in HIF-2α expression in CMSpatients were significantly correlated with EPO and hemoglobin levels. In contrast, the expression of mRNA and protein expression of HIF-1α and EPOR did not differ significantly between the CMS and control patients. Increased MVD was observed in the bone marrow of the patients with CMS and it was significantly correlated with hemoglobin. CONCLUSIONS: Bone marrow cells of CMSpatients may show enhanced activity of the HIF-2α/EPO pathway, and EPO may regulate the erythropoiesis and vasculogenesis through autocrine or/and paracrine mechanisms in the bone marrow niche. The increased MVD in the bone marrow of CMSpatients appears to be involved in the pathogenesis of this disease.
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Authors: Adrianna Moszyńska; Maciej Jaśkiewicz; Marcin Serocki; Aleksandra Cabaj; David K Crossman; Sylwia Bartoszewska; Magdalena Gebert; Michał Dąbrowski; James F Collawn; Rafal Bartoszewski Journal: FASEB J Date: 2022-07 Impact factor: 5.834